Association between Serum Biomarkers with Postoperative Complications and Delay of Adjuvant Chemotherapy Initiation in Ovarian Cancer Patients Undergoing Primary Cytoreductive Surgery: A Pilot Study

Abstract

This study sought to describe and relate the factors associated with complications and delays in adjuvant chemotherapy in patients with ovarian cancer treated with primary cytoreductive surgery. Serum from patients diagnosed with ovarian cancer scheduled for primary cytoreductive surgery were analyzed for prealbumin, 25-OH Vitamin D, intracellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), monocyte chemoattractant protein 2 (MCP-2), macrophage derived chemokine (MDC). Postoperative complications were identified using common terminology criteria for adverse events 4.0 and 30 day after surgery. Delays in adjuvant chemotherapy were defined as >1 week interval between surgery and initiation. Patients with postoperative complications (39.6%) were significantly older, had lower serum prealbumin levels, and higher serum IL-6 and IL-8 than those without. Univariate logistic regression found that age (OR: 1.12, 95%CI: 1.00-1.35) and IL-6 (OR: 1.02, 95%CI: 0.99-1.05) were associated with postoperative complications, whereas age remained significant after multivariate analysis (OR:1.14, 95%CI: 1.00-1.29). Patients with delays in chemotherapy exhibited greater BMI and lower 25-OH Vitamin D than those without. Multivariate analysis found that increasing levels of 25-OH Vitamin D were associated with a lower risk of delayed chemotherapy initiation after controlling for age, body mass index, and tumor grade (OR: 0.93, 95%CI:0.87-0.99). This work suggests that in addition to age being predictive of postoperative complications, serum 25-OH Vitamin D may a provide insight into a patient’s risk for postsurgical delays in chemotherapy initiation. These findings should, however, be confirmed in a larger study including robust survival analysis.

HIGHLIGHTS

1. In a small cohort, increasing age was associated with postsurgical complications in patients with ovarian cancer following primary cytoreductive surgery.

2. In patients with ovarian cancer following primary cytoreductive surgery delays in adjuvant chemotherapy initiation were inversely associated with serum 25-OH vitamin D status.

Acknowledgments

We thank Elangovan Thavathiru for performing the ELISA assays. This project was supported by Gynecological Oncology Section at the Stephenson Cancer Center.

Disclosure Statement

CA reports grants from National Aeronautics and Space Administration, grants from California Strawberry Commission, outside the submitted work. KNM reports personal fees and other from Astra Zeneca, grants, personal fees and other from Genentech/Roche, grants, personal fees and other from Immunogen, grants, personal fees and other from Clovis, grants, personal fees and other from Tesaro, personal fees and other from Pfizer, personal fees from Janssen, personal fees from Aravive, personal fees from VBL Therapeutics, personal fees and other from Onco Med, personal fees from Samumed, grants and other from Lilly, personal fees from Eisai, outside the submitted work. LLH, AW, SH, SKV, DB have nothing to disclose.

Authors’ Contributions

Author contributions include 1) conception and design or analysis and interpretation of data (CJA, LD, ACW, DMB, SKV, KNM, LLH), 2) drafting of the manuscript or revising it critically for important intellectual content (CJA, STH, ACW, KNM, LLM, SKV); and 3) final approval of the manuscript submitted (CJA, LD, ACW, DMB, SKV, STH, KNM, LLH).

Additional information

Funding

This project was supported by Gynecological Oncology Section at the Stephenson Cancer Center. NCI Cancer Center Support Grant (P30 CA225520), the Oklahoma Tobacco Settlement Endowment Trust, and the Johnson Cancer Research Center Research Collaboration of Excellence (CRCE) award.